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Tenascin-C downregulates Wnt inhibitor Dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model

(2013) CELL REPORTS. 5(2). p.482-492
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Abstract
The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic beta-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment.
Keywords
BREAST-CANCER CELLS, EXTRACELLULAR-MATRIX, SIGNALING PATHWAYS, ENDOTHELIAL-CELLS, ANGIOGENIC SWITCH, PROGENITOR CELLS, FOCAL ADHESION, GROWTH, EXPRESSION, FIBRONECTIN

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Chicago
Saupe, Falk, Anja Schwenzer, Yundan Jia, Isabelle Gasser, Caroline Spenlé, Benoit Langlois, Martial Kammerer, et al. 2013. “Tenascin-C Downregulates Wnt Inhibitor Dickkopf-1, Promoting Tumorigenesis in a Neuroendocrine Tumor Model.” Cell Reports 5 (2): 482–492.
APA
Saupe, F., Schwenzer, A., Jia, Y., Gasser, I., Spenlé, C., Langlois, B., Kammerer, M., et al. (2013). Tenascin-C downregulates Wnt inhibitor Dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model. CELL REPORTS, 5(2), 482–492.
Vancouver
1.
Saupe F, Schwenzer A, Jia Y, Gasser I, Spenlé C, Langlois B, et al. Tenascin-C downregulates Wnt inhibitor Dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model. CELL REPORTS. 2013;5(2):482–92.
MLA
Saupe, Falk, Anja Schwenzer, Yundan Jia, et al. “Tenascin-C Downregulates Wnt Inhibitor Dickkopf-1, Promoting Tumorigenesis in a Neuroendocrine Tumor Model.” CELL REPORTS 5.2 (2013): 482–492. Print.
@article{4328549,
  abstract     = {The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic beta-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment.},
  author       = {Saupe, Falk and Schwenzer, Anja and Jia, Yundan and Gasser, Isabelle and Spenl{\'e}, Caroline and Langlois, Benoit and Kammerer, Martial and Lefebvre, Olivier and Hlushchuk, Ruslan and Rupp, Tristan and Marko, Marija and van der Heyden, Michael and Cremel, G{\'e}rard and Arnold, Christiane and Klein, Annick and Simon-Assmann, Patricia and Djonov, Valentin and Neuville-M{\'e}chine, Agn{\`e}s and Esposito, Irene and Slotta-Huspenina, Julia and Janssen, Klaus-Peter and De Wever, Olivier and Christofori, Gerhard and Hussenet, Thomas and Orend, Gertraud},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keyword      = {BREAST-CANCER CELLS,EXTRACELLULAR-MATRIX,SIGNALING PATHWAYS,ENDOTHELIAL-CELLS,ANGIOGENIC SWITCH,PROGENITOR CELLS,FOCAL ADHESION,GROWTH,EXPRESSION,FIBRONECTIN},
  language     = {eng},
  number       = {2},
  pages        = {482--492},
  title        = {Tenascin-C downregulates Wnt inhibitor Dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model},
  url          = {http://dx.doi.org/10.1016/j.celrep.2013.09.014},
  volume       = {5},
  year         = {2013},
}

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